Independent Predictors of Early Death Of

rauma & f T T o re Mica et al., J Trauma Treatment 2012, 1.3 l a t DOI: 10.4172/2167-1222.1000118 a m n

r e

u n o t J Journal of Trauma & Treatment ISSN: 2167-1222

Research Article OpOpenen Access Access Independent Predictors of Early Death of Polytrauma Patients: An Analysis of 696 Patients Ladislav Mica1*, Katja Albrecht1, Marius Keel2 and Otmar Trentz3 1Division of Trauma Surgery, University Hospital of Zürich, Switzerland 2University Hospital of Othopedic Surgery, Inselspital Bern, Switzerland 3Former Head of the Department of Trauma Surgery, University Hospital of Zürich, Switzerland

Abstract Polytrauma patients are at high risk to die due to acute physiological deterioration after a high injury load within the first hours. Trauma scores such as ISS, NISS and APACHE II and laboratory parameters were collected at admission. The aim of this study was to evaluate the independent predictors of early death of the polytrauma patient. A total of 696 patients (age 40.8 ± 15.5 years) who had an ISS ≥ 17 and were admitted to a trauma center within the first 24 hours after trauma were included into this retrospective study. The patients were subdivided into survivors and those who died within the first 72 hours. ISS, NISS and APACHE II score, and laboratory parameters such as lactate, prothrombin time, pH-value, hematocrite, middle arterial pressure and platelets were collected at admission time. Data were compared with Mann-Whitney test and χ2-test for proportions. The data were considered as significant if p < 0.05. Predictive ability was evaluated by using receiver operating characteristic curves. Independent predictors were analyzed by logistic regression analysis. Significantly increased values of ISS, NISS, APACHE II and serum lactate, and significantly decreased values of prothrombin time, middle arterial pressure, hematocrite, Platelets and pH-value were found in the non-survivor group (p < 0.001). APACHE II, NISS, ISS score and the prothrombin time were found to be independent predictive values of death. Early recognition of the risk of death followed by multidisciplinary resuscitation efforts could lead to a better survival rate in the population of polytrauma patients.

Keywords: Polytrauma; ISS; NISS; APACHE II; Prothrombin time an already established or evolving coagulopathy due to trauma. Similar cases were reported in a retrospective study of 1088 [4] patients and Introduction confirmed by other retrospective studies with high case loads [5,6]. The availability of circulatory supportivemedication and scheduled In these studies was a strong correlation between coagulopathy and surgical strategies for the resuscitation of polytrauma patients led to a mortality found, and coagulopathy was identified as an independent better survival outcome. Trauma scoring systems developed during the risk factor [4]. Acute coagulopathy of trauma shock was found to be last decades define the threshold of a polytrauma but do not serve as associated with longer ICU stays [7], with higher risk to develop acute predictive values of death. Independent predictors of an early death renal failure and multiple organ failure (MOF) [7] and with a trend among the widely used trauma scoring systems and commonly available towards acute respiratory distress syndrome [7]. In all these studies the laboratory parameters such as lactate, pH, prothrombin time, platelets transportation time was short and resuscitative fluid management was and hematocrite are not defined yet. The question still remains, which not excessive. Only few studies show the threshold values when to use of the commonly used parameters are the most independent predictors blood products for resuscitation in the polytrauma patients and when to use normal saline [8] depending on ISS, NISS or APACHE II score. of patients’ early death after suffering a polytrauma. The aim isto Independent predictors of the early death are not clearly defined, yet. improve resuscitative procedures and to prevent patient’s early death Little is found in the literature showing clearly a benefit for survival after as a multidisciplinary task. early and aggressive resuscitation with blood products in dependence Trauma scoring systems such as ISS, NISS, and APACHE II define of ISS, NISS or APACHE II score on one hand. On the other hand the level of a polytrauma but do not serve as predictive values of early there seems to be a significant risk to develop an iatrogenic SIRS using death. ISS and NISS describe the severity of trauma depending on the blood-products for resuscitation as shown earlier [9]. This dilemma is anatomical region and injury pattern. The injury pattern describes indirectly the severity of trauma, rendering the patient to higher risk of developing trauma associated diseases such as SIRS. APACHE II score *Corresponding author: Ladislav Mica, Department of Trauma Surgery, uses different physiological and laborytory parameters at admission to University Hospital of Zürich, 8091 Zürich, Switzerland, Tel: 41/ 44 255 41 98; describe the severity of the trauma load on the organism. However, all E-mail: [email protected] polytrauma patients are at high risk to develop an acute coagulopathy Received February 06, 2012; Accepted March 09, 2012; Published March 05, of trauma shock [1,2] in the first few hours after suffering the trauma. 2012 There [3] was a likelihood of 98% found to develop a coagulopathy if the Citation: Mica L, Albrecht K, Keel M, Trentz O (2012) Independent Predictors ISS was above 25 points, the pH-value below 7.1, the core temperature of Early Death of Polytrauma Patients: An Analysis of 696 Patients. J Trauma Treatment 1:118. doi:10.4172/2167-1222.1000118 under 34°C and the systolic blood pressure under 70 mmHg [3]. The traditional description depicts the acute coagulopathy of trauma shock Copyright: © 2012 Mica L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted [1] as a later event mainly caused by resuscitative attempts occurring in use, distribution, and reproduction in any medium, provided the original author and the hospital. There are patients admitted to the emergency room with source are credited.

J Trauma Treatment ISSN: 2167-1222 JTM, an open access journal Volume 1 • Issue 3 • 1000118 Citation: Mica L, Albrecht K, Keel M, Trentz O (2012) Independent Predictors of Early Death of Polytrauma Patients: An Analysis of 696 Patients. J Trauma Treatment 1:118. doi:10.4172/2167-1222.1000118

Page 2 of 5 not solved, yet, but the aim is clear: avoid death of the patient. An early Dickinson, Allschwil, CH). The prothrombin time was measured by a identification of critically incipient trauma coagulopathy according standardized previously described method [16]. to trauma scoring systems and laboratory parameters could lead to a lesser mortality and morbidity in the polytrauma patient. Statistical analysis Continuous data are presented as mean ± standard deviation (SD) In this study the focus was set on widely used trauma scoring- and are compared between groups using the Mann-Whitney test. For systems as a source for the severity of trauma and laboratory proportions the χ2-test was used. All statistical computations were parameters as a sign of an early physiological deterioration. Commonly performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). Results used laboratory parameters were analyzed which may guide physicians’ were considered significant at p < 0.05. Predictive ability of variables decisions during the initial management of a polytrauma patient. The was reported as area under the ROC-curve (AUC) ± standard error. differences in clotting components, i.e. platelets, prothrombin time, Independent predictors were analyzed by stepwise (forward and the values of serum lactate and pH and whole blood parameters such backward) logistic regression analysis. as hematocrite and middle arterial pressure (MAP) were analyzed and compared with the values of survivors and non survivors over the first Results 72 hours. To provide useful information about the predictive value of widely used scoring systems, APACHE II, ISS and NISS scores were Patient population analysed. The aim was to determine independent predictive values of Totally 696 patients with an average age of 40.8 ± 15.5 years were death within the first 72 hours of a polytrauma patient at admission. included into this study. 528 were males and 168 were females. The Materials and Methods overall admission time was 2.0 ± 1.9 hours (2.1 ± 2.2 vs. 1.6 ± 0.9, survivor vs. non-survivor, p = 0.028). Totally 184 (26.4% of all) patients Patients died within the first 72 hours, 135 (27.6 % of males) males and48 (28.4% of females) females (Table 1). 696 polytrauma patients admitted to the emergency room of the University Hospital of Zürich in the time period of the year 1996- ISS, NISS and APACHE II 2002 were enclosed into this study. Admission criteria were an injury severity score (ISS) ≥17 points, age ≥ 16 years and an admission time at The overall ISS of the admitted patients was 35 ± 12.6 points and least 24h after suffering the polytrauma. The patients were subjected to the overall NISS was 43.6 ± 12.3 points (Table 1). The ISS (32.4 ± 11.8 intensive care treatment and damage control surgery. The population vs. 37.8 ± 13.4, survivor vs. non-survivor, p < 0.001) and NISS (41.4 ± was subdivided into two groups: survivors and non survivors of the 13.5 vs. 50.2 ± 14.1, survivor vs. non-survivor, p < 0.001) scores were first 72 hours. All patients’ data were collected retrospectively. ISS, significantly elevated in the patients who did not survive the first 72 NISS and APACHE II were defined according to the data collected at hours (Table 1). Similar predictive powers of ISS (AUC 0.61 ± 0.03; admission to the emergency department. All data were retrieved from Odds-Ratio 0.96) and NISS (AUC 0.68 ± 0.03; Odds-Ratio 1.04) were patient’s sheet according the local Institutional Review Board (IRB) found (Figure 1). APACHE II (15.2 ± 7.9 vs. 25.3 ± 7.7, survivor vs. approval according to the University of Zürich IRB guidelines and non-survivor, p < 0.001) score evaluated at admission was significantly was conducted according to the guidelines of good clinical practice elevated in patients who died within the first 72 hours (Table 1). A high (Retrospektive Analysen in der Chirurgischen Intensivmedizin Nr. StV predictive power (AUC 0.80 ± 0.02; Odds-Ratio 1.15) of the APACHE 01-2008). II score was found at admission (Figure 1). Surgical treatment Lactate acidosis at admission The treatment of all admitted patients followed ®the ATLS Serum lactate (3.0 ± 2.3 vs. 5.6 ± 3.9, survivor vs. non-survivor, guidelines and the previously assessed trauma-management protocol p < 0.001) was evaluated at admission for each patient. The lactate [10-12]. Briefly, after the airway, ventilation and cardiovascular values (AUC 0.73 ± 0.03) (Figure 2) were significantly elevated in management life saving surgery with decompression of body-cavities patients who did not survive the first 72 hours (Table 1). The serum control of hemorrhage and contaminated tissue took place. The first Characteristics Survival over 3 Death within 3 days p-value surgical interventions were followed by stabilization of major fractures days and radical debridement of death tissue. Cefalozoline was used as Number [% of total] 512 (73.6%) 184 (26.4%) ns. † peri-operative antibiotics. In all of the admitted patients an enteral Age [years] 39.1 ± 16.6 45.5 ± 19.2 < 0.001* nutrition was established within 24h after trauma to avoid spontaneous Males [% of Males] 393 (74.4%) 135 (27.6%) ns. † † transmigration of the enteral microbial flora and peritoneal Females [% of Females] 121 (71.6%) 48 (28.4%) ns. ISS [points] 32.4 ± 11.8 37.8 ± 13.4 < 0.001* contamination. NISS [points] 41.4 ± 13.5 50.2 ± 14.1 < 0.001* APACHE II[points] 15.2 ± 7.9 25.3 ± 7.7 < 0.001* Trauma scoring systems Lactate [mmol/L] 3.0 ± 2.31 5.6 ± 3.9 < 0.001* pH 7.31 ± 0.13 7.2 ± 0.2 < 0.001* The Injury Severity Score (ISS) [13] and the New Injury Severity Platelets 192 ± 72.5 152 ± 79.6 < 0.001* Score (NISS) [14] were used to define the severity of trauma. The Acute Prothrombin Time [%] 80.5 ± 19.3 58.9 ± 23.6 < 0.001* Physiology and Chronic Health Evaluation, APACHE II [15] score, was Haematocrite 33.4 ± 7.8 26.4 ± 79.6 < 0.001* MAP 93.2 ± 37.1 79.7 ± 30.0 < 0.001* used to evaluate the overall physiological impairment of the patient. Admission time [h] 2.1 ± 2.2 1.6 ± 0.9 0.028* Laboratory parameters *Mann-Whitney Rank Sum test, † χ2-test. Lactate, pH and hematocrite were measured in intervals with Table 1: Characteristics of patient population (ISS: Injury Severity Score, NISS: New Injury Severity Score, APACHE II: Acute Physiology and Chronic Health a blood-gas analyzer (ABL 800 Flex, Radiometer GmbH, Thalwil, Evaluation). Data are given as mean ± SD, significance was set at p < 0.05, the CH). Platelets were measured by flow cytometry (Facscalibur, Becton data in parentheses are percentage values. *Mann-Whitney test, † χ2-test.

Page 3 of 5

1.0 ± 0.1 vs. 7.2 ± 0.2, survivor vs. non-survivor, p < 0.001) (AUC 0.68 ± APACHE II ISS 0.03) (Figure 2) measured at admission were significantly reduced in NISS patients who did not survive (Table 1). 0.8 Predicted probability Reference line Platelets and prothrombin time

0.6 Significantly decreased platelets (192 ± 75.5 vs. 152 ± 79.6, survivor vs. non-survivor, p < 0.001) (AUC 0.62 ± 0.03) and prothrombin times (80.5 ± 19.3 vs. 58.9 ± 23.6, survivor vs. non-survivor, p < 0.001) (AUC

0.4

Sensitivity 0.76 ± 0.02; Odds-Ratio 0.98) (Figure 3) were found in patients who did not survive the first 72 hours (Table 1). After resuscitation and damage control surgery the values were mostly normalized without significant 0.2 differences after 24 hours (data not shown). Blood loss 0.0 0.0 0.2 0.4 0.6 0.8 1.0 Haematocrite-values (33.4 ± 7.8 vs. 26.4 ± 7.9, survivor vs. non- 1 - Specificity survivor, p < 0.001) and middle arterial blood pressure (MAP) (93.2 AUC (CI: 95%) ± 37.1 vs. 79.7 ± 30.0, survivor vs. non-survivor, p < 0.001) were APACHE II 0.80 ± 0.02 (0.75, 0.84) measured at admission of the patients. As expected, these values were ISS 0.61 ± 0.03 (0.54, 0.66) significantly (Table 1) reduced in patients who died within thefirst

NISS 0.68 ± 0.03 (0.63, 0.74) 72 hours (Haematocrite: AUC 0.64 ± 0.03, MAP: AUC 0.65 ± 0.03)

Predicted probability 0.85 ± 0.02 (0.81, 0.88) (Figure 4).

Figure 1: ROC curve of APACHE II (AUC 0.80 ± 0.02; Odds-Ratio 1.15), ISS Independent predictors of death: ISS, NISS, APACHE II and (AUC 0.61 ± 0.03; Odds-Ratio 0.96), and NISS (AUC 0.68 ± 0.03; Odds-Ratio prothrombin time 1.04). The patients were evaluated by the scoring systems ad admission. All scores of the patients who did not survive were significantly elevated (p < In a stepwise logistic regression including all significant parameters 0.001). Predicted probability of death based on all four independent predictors (APACHE II, ISS, NISS and prothrombin time (Figure 3.)) results in a very good above, APACHE II, NISS, ISS score and the prothrombin time were predictive probability. Data are given as area under the curve (AUC) and 95% found to be independent predictors of death. The combination confidence interval (CI: 95%) with it’s with (lower bound, upper bound). “predicted probability” of these variables thus is a significantly better predictor than each single score (AUC 0.85 ± 0.02) (Figure 1)

1.0 Lactate Discussion pH Reference line Massive bleeding is the key issue in trauma and emergency surgery 0.8

1.0 Prothrombin time Platelets 0.6 Reference line 0.8

0.4 Sensitivity 0.6

0.2 0.4 Sensitivity

0.0 0.0 0.2 0.4 0.6 0.8 1.0 0.2 1 - Specificity

AUC ( CI: 95% ) 0.0 0.0 0.2 0.4 0.6 0.8 1.0 Lactate 0.73 ± 0.03 (0.68, 0.78) 1 - Specificity pH 0.68 ± 0.03 (0.62,0.73) AUC ( CI: 95% ) Figure 2: ROC curve of serum lactate and pH values, measured ad admission. Prothrombin time 0.76 ± 0.02 (0.71, 0.80) Both values were significantly different between surviving and non-surviving patients (p < 0.001). Thus, the predictive ability of serum lactate and pH-value Platelets 0.62 ± 0.03 (0.57, 0.68) revealed no independency in the multiple logistic regression analysis. The predictive ability of pH and lactate is quite poor; hence pH is already contained Figure 3: ROC curve of prothrombin time and platelets, measured ad in the APACHE II score. Data are given as area under the curve (AUC) and admission. Both parameters were significantly different between survivors and 95% confidence interval (CI: 95%) with it’s with (lower bound, upper bound). non-survivors (p < 0.001). Prothrombin time (AUC 0.76 ± 0.02; Odds-Ratio 0.98) evolved as an independent predictive value of death within the first 72 hours. In the case of a polytrauma patient the prothrombin time has a higher lactate concentrations were normalized after resuscitation and damage predictive value than platelet count. Data are given as area under the curve control surgery after 24 hours. There were no significant differences of (AUC) and 95% confidence interval (CI: 95%) with it’s with (lower bound, upper lactate values found between groups after 24 hours. The pH values (7.31 bound).

Page 4 of 5

1.0 MAP amount of activated protein C [21] and thus inhibiting the clotting HKT cascade. However, these assumptions still remain speculative. Reference line 0.8 APACHE II: physiological changes due to traumatic hemorrhage and tissue destruction Metabolic lactate acidosis accompanied by hypothermia lowers 0.6 the functionality of blood clotting factors supporting progressive bleeding. The activity of the prothrombinase complex (FXa/FVa) is

0.4 reduced by 50% at pH 7.2, by 70% at pH 7.0 and by 90% at pH 6.8 Sensitivity [22,23]. Most of the factors involved in blood clotting are severely impaired in function when the pH is lower than 7.1: probably due 0.2 to reduced affinity of2+ Ca binding sites. Hypothermia inhibits any enzymatic activity according to the equation of Arrhenius and van’t Hoff and dilution during resuscitation and hypothermia favors 0.0 0.0 0.2 0.4 0.6 0.8 1.0 ongoing bleeding. Hypothermia supports lactate acidosis by the above 1 - Specificity mentioned mechanism. Clinically significant changes in blood clotting are already observed at temperatures under 34°C (93.2°F) [23,24] even AUC ( CI: 95% ) if the concentration of clotting factors has no pathological changes. MAP 0.65 ± 0.03 (0.59, 0.71) When the core temperature falls below 33°C (91.4°F) in a polytrauma HKT 0.64 ± 0.03 (0.58, 0.70) patient the activity of the blood-clotting system falls below 50% even if there is a normal factor concentration and functionality [24]. Higher Figure 4: ROC curve of middle arterial pressure (MAP) and hematocrite (HKT), measured at admission. Both parameters were significantly different between APACHE II scores significantly increased the risk of death within the survivors and non-survivors (p < 0.001). The data revealed poor predictive first 72 hours after admission. Early and aggressive resuscitative efforts value of MAP and HKT, certainly when massively lowered death might be with restoring patient’s physiology especially blood coagulation and unenviable. Data are given as area under the curve (AUC) and 95% confidence interval (CI: 95%) with it’s with (lower bound, upper bound). acidosis could improve the survival outcome. Acidosis [17,18]. The availability of resuscitative components such as red blood cells, platelets and fresh frozen plasma does not guarantee the survival Lactate acidosis in the polytrauma patient roots in several problems: of a polytrauma patient with a massive hemorrhage after suffering a hypothermia, anemia and lactate acidosis itself. The kidney and the trauma. The data presented in this study show independent predictive respiratory system usually fail to correct the acidosis in polytrauma and shocked patients. Corrective resuscitative interventions with e.g. parameters such as ISS, NISS, APACHE II and prothrombin time for sodium bicarbonate (NaHCO ) and tris-hydroxymethylaminomethane the posttraumatic death within the first 72 hours after admission to a 3 (THAM) may restore normal pH, furthermore, they seems to have a level I trauma center. Probably, pointing on decision guiding values. thrombo-permissive effect [25,26]. Acidosis increases the fibrinogen Normally, the operative mortality is low for most of the surgical degradation by the factor 1.8 and thus leads to prolonged bleeding [27]. interventions, ranging from < 0.1% to 8% [19]. Unexpected acute Parallely, the platelets are also inhibited by lover blood pH. However, bleeding during surgical interventions may raise the mortality over how acidosis leads to decreased thrombocyte counts is not fully 20% [19]. Literature lacks clear evidenced procedures and independent understood, yet. Transfusion of packed red blood cells may aggravate predictive parameters to estimate the risk of early death and to posttraumatic acidosis due to a lower base excess acquired during avoid hemorrhage in polytrauma patients. This seems not to be very storage time [28]. There seems to be a general inhibition of all cellular surprising due to the wide heterogeneity of this field. functions during acidosis. Even when the pH-values reached a similar ISS and NISS: tissue destruction bleeds level after 24 hours the suppressive effect on physiological functions of acidosis could be long-termed. Trauma leads to destruction of tissue and blood loss. The demonstrated data show significantly higher values in both scoring Platelets systems comparing the survival to the non-survival group, according There is evidence to keep platelet counts above 50 – 100 x 109/L in to the severity of tissue destruction. Tissue destruction leads to the the polytrauma patient [29]. The shown platelet counts in this study set free of the Kininogene and Kallikrein leading to the activation of show levels above 100 x 109/L also in patients who died within the first the factor XII (Hageman-factor) [20]. Systemic spread of Kininogene 72 hours after admission. Platelets and red blood cells have to be in a and Kallikrein may activate systemically the factor XII leading to a certain relation to allow optimal thrombocyte function. Thrombocyte consumptive coagulopathy. However, the mechanism how trauma function is reduced during acidosis with a permissive effect on ongoing coagulopathy develops remains uncertain. Other theories point on bleeding. Thombocytes measured after 24 hours (data not shown) the rise of soluble thrombomodulin and fall in protein C levels after had similar values in all groups pointing on a possible long-term trauma [20]. This may be correlated with the development of acute effect, probably caused by acidosis. Platelet loss may be attributed to coagulopathy of trauma shock [1]. Protein C is a natural anticoagulant consumption at trauma site and to loss of whole blood. excessively consuming plasminogen activator inhibitor (PAI-1) [20,2]. The correlation between rise of PAI-1 and decrease of protein C level Prothrombin time were shown elsewhere [2]. Theoretically the increase in membrane- Significant reduction of the prothrombin time in patients who did bound thrombomodulin on endothelial cells may lead to scavenging not survive may be caused by hypothermia, acidosis and dilution or of thrombin, reducing its amount to produce fibrin and raising the activation-decay [30]. The main reason for the reduction of the values

Page 5 of 5 cannot be identified here. The acidosis correlates with the reduction unstable patients. In: Goris RJA, Trentz O The integrated approach to trauma of the prothrombin time, as discussed earlier. Dilution of the blood care, the first 24 hours. Springer 172-178. coagulation cascade during resuscitative attempts has not to be 12. Collicott PE, Hughes I (1980) Training in advanced trauma life support. JAMA considered due to very low rescue-times and low resuscitative volumes 243: 1156-1159. of cristaloids. Further more, the loss of whole blood and acidosis seem 13. Baker SP, O’Neill B, Haddon W Jr, Long WB (1974) The injury severity score: A to be the core reasons for reduced prothrombin times and for the method for describing patients with multiple injuries and evaluating emergency independence as a predictor of death. care. J Trauma 14: 187-196. 14. Champion HR, Copes WS, Sacco WJ, Lawnick MM, Bain LW, et al. (1990) A Hematocrite new characterization of injury severity. J Trauma 30: 539-545. The decreased hematocrite values favor the development of 15. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a acidosis. Lowered haematocrite is a double cutting edge, it favors severity of disease classification system. Crit Care Med 13: 818-829. hypoxemia and an anaerobic metabolism resulting in lactate acidosis 16. Jackson CM, White GC (2001) Scientific and standardization committee and the reduction of haemoglobin reduces also the main blood buffer communication: a reference system approach to future standardization of laboratory tests for hemostasis. system [31]. The data shown in this study suggest hemorrhage as a death factor. Taken to gather lower hematocrite-values favor the genesis 17. Sauaia A, Moore FA, Moore EE, Lezotte DC (1996) Early risk factors for of lactate acidosis [31], acidosis itself inhibits the blood coagulation postinjury multiple organ failure. World J Surg 20: 392-400. cascade and probably also the normal function of platelets. There is 18. Stewart RM, Myers JG, Dent DL, Ermis P, Gray GA, et al. (2003) Seven evidence that early and aggressive resuscitation with FFP (fresh frozen hundred fifty-three consecutive deaths in a level 1 trauma center: the argument for injury prevention. J Trauma 54: 66-70. plasma) and red blood cells (RBC) improves the ICU outcome of the polytrauma patient [32,33]. The very early normalization of the blood- 19. Copeland GP, Jones D, Walters M (1991) POSSUM: a scoring system for clotting pathway could lead to a better survival ratio as seen in military surgical audit. Br J Surg 78: 355-360. trauma settings [33]. 20. Bryant JW, Shariat-Madar Z (2009) Human plasma kallikrein-kinin system: physiological and biochemical parameters. Cardiovasc Hematol Agents Med Conclusions Chem 7: 234-250. 21. Roberts HR, Hoffman M, Monroe DM (2006) A cell-based model of thrombin The APACHE II, ISS and NISS scores with the prothrombin time as generation. Semin Thromb Hemost 32: 32-38. independent predictive values of death can be used to guide surgeons’ decisions during the management of an acute polytrauma patient. 22. Meng ZH, Wolberg AS, Monroe DM 3rd, Hoffman M (2003) The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy This data show that the very early management of polytrauma patient, of high-dose factor VIIa in hypothermic and acidotic patients. J Trauma 55: according to the independent predictive factors could improve the 886-891. outcome of the polytrauma patient. This proves the ‘golden hour’ in 23. Lier H, Krep H, Schroeder S, Stuber F (2008) Preconditions of hemostasis the treatment of trauma shock. in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma. J Trauma 65: 951-960. References 24. Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, et al. (2008) The 1. Frith D, Brohi K (2010) The acute coagulopathy of trauma shock: clinical coagulopathy of trauma: a review of mechanisms. J Trauma 65: 748-754. relevance. Surgeon 8: 159-163. 25. Martini WZ, Dubick MA, Wade CE, Holcomb JB (2007) Evaluation of tris 2. Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, et al. (2007) Acute hydroxymethylaminomethane on reversing coagulation abnormalities caused traumatic coagulopathy: initiated by hypoperfusion: modulated through the by acidosis in pigs. Crit Care Med 35: 1568-1574. protein C pathway? Ann Surg 245: 812-818. 26. Martini WZ, Dubick MA, Pusateri AE, Park MS, Ryan KL, et al. (2006) Does 3. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, et al. (1997) bicarbonate correct coagulation function impaired by acidosis in swine? J Predicting life-threatening coagulopathy in the massively transfused trauma Trauma 61: 99-106. patient: hypothermia and acidoses revisited. J Trauma 42: 857-861. 27. Martini WZ (2009) Coagulopathy by hypothermia and acidosis: mechanisms of 4. Brohi K, Singh J, Heron M, Coats T (2003) Acute traumatic coagulopathy. J thrombin generation and fibrinogen availability. J Trauma 67: 202-208. Trauma 54: 1127-1130. 28. Raat NJ, Berends F, Verhoeven AJ, de Korte D, Ince C (2005) The age of 5. MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M (2003) Early stored red blood cell concentrates at the time of transfusion. Transfus Med 15: coagulopathy predicts mortality in trauma. J Trauma 55: 39-44. 419-423. 6. Maegele M, Lefering R, Yucel N, Tjardes T, Rixen D, et al. (2007) Early coagulopathy in multiple injury: an analysis from the German trauma registry 29. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Ferna, et al. (2010) on 8724 patients. Injury 38: 298-304. Management of bleeding following major trauma: an updated European guideline. Crit Care 14: R52. 7. Salim A, Martin M, Constantinou C, Sangthong B, Brown C, et al. (2006) Acute respiratory distress syndrome in the trauma intensive care unit: Morbid but not 30. Bolliger D, Szlam F, Levy JH, Molinaro RJ, Tanaka KA (2010) Haemodilution- mortal. Arch Surg 141: 655-658. induced profibrinolytic state is mitigated by fresh-frozen plasma: implications for early haemostatic intervention in massive haemorrhage. Br J Anaesth 104: 8. Hagiwara A, Kimura A, Kato H, Mizushima Y, Matsuoka T, et al. (2010) 318-325. Hemodynamic reactions in patients with hemorrhagic shock from blunt trauma after initial fluid therapy. J Trauma 69: 1161-1168. 31. Chiarla C, Giovannini I, Giuliante F, Vellone M, Ardito F, et al. (2010) Significance of hemoglobin concentration in determining blood CO2 binding 9. Beale E, Zhu J, Chan L, Shulman I, Harwood R, et al. (2006) Blood transfusion capacity in critical illness. Respir Physiol Neurobiol 172: 32-36. in critically injured patients: a prospective study. Injury 37: 455-465. 32. Sihler KC, Napolitano LM (2009) Massive transfusion: new insights. Chest 136: 10. Ertel W, Trentz O (1995) Causes of shock in the severely traumatized patient: 1654-1667. emergency treatment. In: Goris RJA, Trentz O The integrated approach to trauma care, the first 24 hours. Springer 78-87. 33. Kashuk JL, Moore EE, Johnson JL, Haenel J, Wilson M, et al. (2008) Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma: packed red blood 11. Trentz O, Friedl HP (1995) Therapeutic sequences in the acute period in cells the answer? J Trauma 65: 261-270.

J Trauma Treatment ISSN: 2167-1222 JTM, an open access journal Volume 1 • Issue 3 • 1000118